ABSTRACT
Whether neuromuscular activity influences the size of motor nerves is controversial. All neuromuscular activity in cat hindlimbs was eliminated by spinal cord isolation (SCI), namely, spinal cord transection above and below the medial gastrocnemius (MG) and soleus (SOL) motoneuron pools and L5-S3 dorsal root transection. MG, SOL and sural (SUR) nerves were removed for size measurements, eight months after SCI surgery and from age-matched control cats. Nerve fiber number, the linear relationship between axon size and myelin thickness, and the bimodal distributions of nerve fiber area and diameter were maintained in all three nerves after SCI. The distributions of myelinated sensory fibers were unchanged in SUR nerves in contrast to the myelinated motor fibers in the MG and SOL nerves that were significantly larger. These findings provide evidence that all lumbar motoneurons survive SCI and that their nerve fibers enlarge. Thus, motor nerve fiber size in addition to the properties of the motoneurons and their muscle fibers is dynamic, responding to neuromuscular activity.
ABSTRACT
Periodontal diseases manifest by the formation of deep pockets between the gingiva and teeth where multispecies bacterial biofilms flourish, causing inflammation and bone loss. Epithelial cell receptor αvß6 integrin that regulates inflammation by activating the anti-inflammatory cytokine transforming growth factor-ß1, is highly expressed in healthy junctional epithelium that connects the gingiva to the tooth enamel. However, its expression is attenuated in human periodontal disease. Moreover, Itgb6 -/- mice display increased periodontal inflammation compared to wild-type mice. We hypothesized that bacterial biofilms present in the periodontal pockets suppress αvß6 integrin levels in periodontal disease and that this change aggravates inflammation. To this end, we generated three-week-old multi-species oral biofilms in vitro and treated cultured gingival epithelial cells (GECs) with their extracts. The biofilm extracts caused suppression of ß6 integrin expression and upregulation of pro-inflammatory cytokines, including interleukin-1ß and -6. Furthermore, GECs with ß6 integrin siRNA knockdown showed increased interleukin-1ß expression, indicating that αvß6 integrin-deficiency is associated with pro-inflammatory cytokine responsiveness. FSL-1, a synthetic bacterial lipopeptide, also suppressed ß6 integrin expression in GECs. Therefore, biofilm components, including lipopeptides, may downregulate αvß6 integrin expression in the pocket epithelium and thus promote epithelial cell-driven pro-inflammatory response in periodontal disease.
